Actinonin is a known antibacterially active compound which is described in some literatures (see "I.A.M. Symposia on Microbiology, No. 6, Chemistry of Microbial Product" pp. 204-214 (1964) and U.S. Pat. No. 3,240,787 specification) and which is an antibiotic produced by cultivation of a Streptomyces strain (identified as ATCC 14,903 or NCIB 8845). Physicochemical properties of actinonin are alredy known. Actinonin is a compound having the structural formula ##STR1##
Further, it is known that actinonin exhibits an activity inhibitory to aminopeptidase M, that actinonin is effective as an immunopotentiating agent (Japanese patent application first publication "Kokai" No. 15840/86 and U.S. Pat. No. 4,663,342) and that actinonin is effective as an analgesic agent (Japanese patent application first publication "Kokai" No. 4228/87).
Furthermore, angiogenesis or neovascularization, that is, the development of blood vessels in a mammal takes place through the biological processes comprising migration of vascular endothelial cells, proliferation of these cells and formation of capillary tubes. It is expectable that such diseases having the accompanying angiogenesis, for instance diabetic retinopathy and inflammatory responses can be treated therapeutically by inhibiting the angiogenesis, and it is apparent that a chemical compound which inhibits the angiogenesis would have an adverse effect upon the development of the diabetic retinopathy and inflammatory response (see, for example, U.S. Pat. No. 4,552,888 specification).
We have made researches in an attempt to detect and provide such chemical substances which exhibit an activity inhibitory to the angiogenesis in a mammal, and as a result, we have now found that actinonin shows a remarkably high activity to inhibit the angiogenesis.
This discovery that actinonin shows an angiogenesis-inhibiting activity is a first finding which is now obtained through researches by the present inventors.